Water → HCID 66673627, compound

HRID 423649Notes

Reaction equation

HRID 423649 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([S:8][CH3:9])[CH:5]=[CH:4][C:3]=1[C:10]1[N:11]=[CH:12][C:13]([OH:16])=[N:14][CH:15]=1.CS(O[CH2:22][CH:23]1[CH2:28][CH2:27][N:26]([C:29]2[O:33][N:32]=[C:31]([CH:34]([CH3:36])[CH3:35])[N:30]=2)[CH2:25][CH2:24]1)(=O)=O.C([O-])([O-])=O.[K+].[K+].O>CN(C=O)C>[F:1][C:2]1[CH:7]=[C:6]([S:8][CH3:9])[CH:5]=[CH:4][C:3]=1[C:10]1[CH:15]=[N:14][C:13]([O:16][CH2:22][CH:23]2[CH2:28][CH2:27][N:26]([C:29]3[O:33][N:32]=[C:31]([CH:34]([CH3:36])[CH3:35])[N:30]=3)[CH2:25][CH2:24]2)=[CH:12][N:11]=1

Participants

6

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 57930198(1-(3-Isopropyl-1,2,4-oxadiazol-5-yl)piperidin-4-yl)methyl methanesulfonateHCID 178503116HCID 178503116, compound

Product 1

HCID 66673627HCID 66673627, compoundYield 44%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture of 5-[2-fluoro-4-(methylthio)phenyl]-2-pyrazinol (and tautomers thereof) (0.35 g, 1.48 mmol), {1-[3-(1-methylethyl)-1,2,4-oxadiazol-5-yl]-4-piperidinyl}methyl methanesulfonate (prepared as in Example 100, Step 4, 0.61 g, 2.0 mmol) and K2CO3 (0.42 g, 2.96 mmol) in DMF (14 mL) was stirred at 100° C. in a preheated oil bath for 5 h. The mixture was cooled to ambient temperature, treated with water, and the mixture was extracted with EtOAc (70 mL×2). The combined organic extracts were washed with water, brine and dried over Na2SO4, filtered, and the filtrate was concentrated to a brown solid, which was purified by chromatography on a silica gel column eluted with 1:25 acetone/CH2Cl2 to give 2-[2-fluoro-4-(methylthio)phenyl]-5-[({1-[3-(1-methylethyl)-1,2,4-oxadiazol-5-yl]-4-piperidinyl}methyl)oxy]pyrazine (0.3 g, 44% yield) as a light beige solid. 1H NMR (400 MHz, CDCl3): δ 8.54 (s, 1H), 8.28 (d, 1H, J=1.3 Hz), 7.86 (t, 1H, J=8.3 Hz), 7.10 (dd, 1H, Ja=8.3 Hz, Jb=1.7 Hz), 7.00 (dd, 1H, Ja=12.1 Hz, Jb=1.9 Hz), 4.30-4.20 (m, 4H), 3.20-3.05 (m, 2H), 2.92 (septet, 1H, J=7.0 Hz), 2.50 (s, 3H), 2.20-2.05 (m, 1H), 2.00-1.90 (m, 2H), 1.55-1.40 (m, 2H), 1.29 (d, 6H, J=6.9 Hz); LRMS (ESI), m/z 444 (M+H).

Workup

  1. extractionthe mixture was extracted with EtOAc (70 mL×2)
  2. washThe combined organic extracts were washed with water, brine
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationthe filtrate was concentrated to a brown solid, which
  6. customwas purified by chromatography on a silica gel column
  7. washeluted with 1:25 acetone/CH2Cl2

Sources & evidence

ORD record
ord-20daaa52d0204702830eb278309e0aaa
Source dataset
uspto-grants-2012_01
Patent number
US08101634B2

Reaction notes

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